pyrrolidine-1-carbonitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the manner given in Example 2, 1-pyrrolidinecarbonitrile is treated with sodium methoxide in methanol to give methyl 1-pyrrolidinecarboximidate.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the manner given in Example 2, 1-pyrrolidinecarbonitrile is treated with sodium methoxide in methanol to give methyl 1-pyrrolidinecarboximidate.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product of step (b) (2.22 g, 0.00948 moles) was dissolved in 15 ml chlorobenzene. N,N-diethylaniline hydrobromide (2.18 g, 0.00948 moles) was added followed by 1-pyrrolidinecarbonitrile (1.37 g, 0.01422 moles). A catalytic amount of 4-dimethylaminopyridine was added and the reaction heated to reflux for 6 hours. The reaction was then cooled to room temperature and diluted with 100 ml ethyl acetate. A sticky oil precipitated from solution and was stirred for 24 hours. The resulting solids were filtered and recrystallized from hot isopropanol to give the N-(4(2-((4-morpholinyl)carbonyl)ethyl)phenyl)-1-pyrrolidinecarboximidamide hydrobromide, M.P. 207-209° C. the reaction heated to reflux for 6 hours A sticky oil precipitated from solution The resulting solids were filtered recrystallized from hot isopropanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product of step (b) (2.22 g, 0.00948 moles) was dissolved in 15 ml chlorobenzene. N,N-diethylaniline hydrobromide (2.18 g, 0.00948 moles) was added followed by 1-pyrrolidinecarbonitrile (1.37 g, 0.01422 moles). A catalytic amount of 4-dimethylaminopyridine was added and the reaction heated to reflux for 6 hours. The reaction was then cooled to room temperature and diluted with 100 ml ethyl acetate. A sticky oil precipitated from solution and was stirred for 24 hours. The resulting solids were filtered and recrystallized from hot isopropanol to give the N-(4(2-((4-morpholinyl)carbonyl)ethyl)phenyl)-1-pyrrolidinecarboximidamide hydrobromide, M.P. 207-209° C. the reaction heated to reflux for 6 hours A sticky oil precipitated from solution The resulting solids were filtered recrystallized from hot isopropanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the product of step (a), 2.3 g, 0.0135 moles. in 35 ml of chlorobenzene was added 4-dimethylaminopyridine. To this was added 1-pyrrolidinecarbonitrile, 1.2 ml, 0.006 moles, and the reaction was heated to reflux for 8 hours. The reaction cooled to room temperature and the solvent was decanted. To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate. A solid crystallized and was collected by filtration. The above solid was then dried at 80° C. for 24 hours giving N-(3-(((propyl)carbonyl)amino)phenyl)-1-pyrrolidinecarboximidamide hydrochloride, 1.5 g, m.p. 207-208° C. the reaction was heated to reflux for 8 hours the solvent was decanted To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate A solid crystallized was collected by filtration The above solid was then dried at 80° C. for 24 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the product of step (a), 2.0 g, 0.006 moles, in 35 ml of chlorobenzene was added 4-dimethylaminopyridine. To this was added 1-pyrrolidinecarbonitrile, 1.5 ml; 0.008 moles, and the reaction was heated to reflux for 4 hours. The reaction cooled to room temperature and the solvent was decanted. To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate. A solid crystallized and was collected by filtration. The above solid was then dried at 80° C. for 24 hours to give N-[3-(((4-phenylbutyl)amino)carbonyl)phenyl]-1-pyrrolidinecarboximidamide hydrochloride, 2.3 g, m.p. 197-198° C. 0.008 moles, and the reaction was heated to reflux for 4 hours the solvent was decanted To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate A solid crystallized was collected by filtration The above solid was then dried at 80° C. for 24 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the product of step (a), 2.0 g, 0.006 moles, in 35 ml of chlorobenzene was added 4-dimethylaminopyridine. To this was added 1-pyrrolidinecarbonitrile, 1.5 ml; 0.008 moles, and the reaction was heated to reflux for 4 hours. The reaction cooled to room temperature and the solvent was decanted. To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate. A solid crystallized and was collected by filtration. The above solid was then dried at 80° C. for 24 hours to give N-[3-(((4-phenylbutyl)amino)carbonyl)phenyl]-1-pyrrolidinecarboximidamide hydrochloride, 2.3 g, m.p. 197-198° C. 0.008 moles, and the reaction was heated to reflux for 4 hours the solvent was decanted To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate A solid crystallized was collected by filtration The above solid was then dried at 80° C. for 24 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the product of step (a), 2.0 g, 0.006 moles, in 35 ml of chlorobenzene was added 4-dimethylaminopyridine. To this was added 1-pyrrolidinecarbonitrile, 1.2 ml, 0.06 moles, and the reaction was heated to reflux for 4 hours. The reaction was cooled to room temperature and the solvent decanted. To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate. A solid crystallized and was collected by filtration. The above solid was then dried at 60° C. for 24 hours giving 700 mg of N-(3-(((2-phenylethyl)carbonyl)amino)phenyl)-1-pyrrolidinecarboximidamide hydrochloride, m.p. 220-221° C. the reaction was heated to reflux for 4 hours the solvent decanted To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate A solid crystallized was collected by filtration The above solid was then dried at 60° C. for 24 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the product of step (a), 2.0 g, 0.006 moles, in 35 ml of chlorobenzene was added 4-dimethylaminopyridine. To this was added 1-pyrrolidinecarbonitrile, 1.2 ml, 0.06 moles, and the reaction was heated to reflux for 4 hours. The reaction was cooled to room temperature and the solvent decanted. To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate. A solid crystallized and was collected by filtration. The above solid was then dried at 60° C. for 24 hours giving 700 mg of N-(3-(((2-phenylethyl)carbonyl)amino)phenyl)-1-pyrrolidinecarboximidamide hydrochloride, m.p. 220-221° C. the reaction was heated to reflux for 4 hours the solvent decanted To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate A solid crystallized was collected by filtration The above solid was then dried at 60° C. for 24 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Samples of 3-nitroaniline hydrochloride, 15.5 g, and 1-pyrrolidinecarbonitrile, 9.6 g, were combined with 12 ml of chlorobenzene, and the mixture was warmed to reflux for three hours, and then allowed to cool. The resulting solid mass was taken up in 200 ml of hot water, and the chlorobenzene layer was separated. The aqueous layer was washed with 30 ml of chloroform and the combined organic layers were washed with 50 ml of water. The aqueous layers were combined, warmed, treated with charcoal and filtered hot. The filtrate was allowed to cool, and made strongly basic with 50% sodium hydroxide. This basic mixture was extracted with 200 ml of chloroform. The chloroform extract was concentrated on a steam bath to 150 ml, then diluted with hexanes to 300 ml, and stirred until yellow solids formed, giving 17 g of the N-(3-nitrophenyl)-1-pyrrolidinecarboximidamide. m.p. 117-118° C. the mixture was warmed to reflux for three hours to cool the chlorobenzene layer was separated The aqueous layer was washed with 30 ml of chloroform the combined organic layers were washed with 50 ml of water warmed treated with charcoal filtered hot to cool This basic mixture was extracted with 200 ml of chloroform The chloroform extract was concentrated on a steam bath to 150 ml diluted with hexanes to 300 ml formed

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Samples of 3-nitroaniline hydrochloride, 15.5 g, and 1-pyrrolidinecarbonitrile, 9.6 g, were combined with 12 ml of chlorobenzene, and the mixture was warmed to reflux for three hours, and then allowed to cool. The resulting solid mass was taken up in 200 ml of hot water, and the chlorobenzene layer was separated. The aqueous layer was washed with 30 ml of chloroform and the combined organic layers were washed with 50 ml of water. The aqueous layers were combined, warmed, treated with charcoal and filtered hot. The filtrate was allowed to cool, and made strongly basic with 50% sodium hydroxide. This basic mixture was extracted with 200 ml of chloroform. The chloroform extract was concentrated on a steam bath to 150 ml, then diluted with hexanes to 300 ml, and stirred until yellow solids formed, giving 17 g of the N-(3-nitrophenyl)-1-pyrrolidinecarboximidamide. m.p. 117-118° C. the mixture was warmed to reflux for three hours to cool the chlorobenzene layer was separated The aqueous layer was washed with 30 ml of chloroform the combined organic layers were washed with 50 ml of water warmed treated with charcoal filtered hot to cool This basic mixture was extracted with 200 ml of chloroform The chloroform extract was concentrated on a steam bath to 150 ml diluted with hexanes to 300 ml formed

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the product of step (a), 2.0 g, 0.006 moles, in 35 ml of chlorobenzene was added 4-dimethylaminopyridine. To this was added 1-pyrrolidinecarbonitrile, 1.5 ml; 0.008 moles, and the reaction was heated to reflux for 4hours. The reaction cooled to room temperature and the solvent was decanted. To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate. A solid crystallized and was collected by filtration. The above solid was then dried at 80° C. for 24 hours to give N-[3-(((4-phenylbutyl)amino)carbonyl)phenyl]-1-pyrrolidinecarboximidamide hydrochloride, 2.3 g, m.p. 197°-198° C. 0.008 moles, and the reaction was heated to reflux for 4hours the solvent was decanted To the residue was added 25 ml of isopropanol and 150 ml of ethyl acetate A solid crystallized was collected by filtration The above solid was then dried at 80° C. for 24 hours